Combined Risk Allele Score of Eight Type 2 Diabetes Genes Is Associated With Reduced First Phase Glucose Stimulated Insulin Secretion During Hyperglycemic Clamps

L.M. Hart, A.M.C. Bik-Simonis, G. Nijpels, T.W. van Haeften, S.A. Schäfer, J.J. Houwing-Duistermaat, D.I. Boomsma, M.J. Groenewoud, E. Reiling, E.C. van Hove, M. Diamant, M.H.H. Kramer, R.J. Heine, J.A. Maassen, K. Kirchhoff, F. Machicao, H.U. Häring, P.E. Slagboom, G. Willemsen, E.M.W. EekhoffE.J.C. de Geus, J.J.M. Dekker, A. Fritsche

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OBJECTIVE - At least 20 type 2 diabetes loci have now been identified, and several of these are associated with altered β-cell function. In this study, we have investigated the combined effects of eight known β-cell loci on insulin secretion stimulated by three different secretagogues during hyperglycemic clamps. RESEARCH DESIGN AND METHODS - A total of 447 subjects originating from four independent studies in the Netherlands and Germany (256 with normal glucose tolerance [NGT]/ 191 with impaired glucose tolerance [IGT]) underwent a hyperglycemic clamp. A subset had an extended clamp with additional glucagon-like peptide (GLP)-1 and arginine (n = 224). We next genotyped single nucleotide polymorphisms in TCF7L2, KCNJ11, CDKAL1, IGF2BP2, HHEX/IDE, CDKN2A/B, SLC30A8, and MTNR1B and calculated a risk allele score by risk allele counting. RESULTS - The risk allele score was associated with lower first-phase glucose-stimulated insulin secretion (GSIS) (P = 7.1 × 10
Original languageEnglish
Pages (from-to)287-292
Issue number1
Publication statusPublished - 2010

Cohort Studies

  • Netherlands Twin Register (NTR)

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